The primary objective is to utilize our generated anti-human leukemia monoclonal antibodies (McAbs) to develop new therapeutic means (e.g., idiotype vaccines), to study immunological, biological and biochemical properties of the leukemia antigens, to find new clues as to the pathogenesis of human leukemia, and to effectively use in the diagnosis and in the monitoring of leukemia patients. In the generation of the anti-leukemia McAbs, we are expanding our earlier success in generating anti-T leukemia McAbs into generating anti-non-T leukemia McAbs. Thus, anti-leukemia McAbs are being generated by a very efficient and unconventional approach. In this approach, immunologically-active human leukemia associated cell membrane antigens are isolated from large quantities (e.g., 5 X 1010 cells) of human leukemia cells of different phenotypes (i.e., T, pre-B and non-T/non-B) by use of a novel purification system. The isolated antigens are being successfully utilized to generate anti-leukemia McAbs. Through this unconventional approach to generating anti-leukemia McAbs, we have generated many (over 20) McAbs directed toward several different leukemia-associated cell surface antigens. Some of these McAbs show strikingly high specificity for leukemia cells and define unique leukemia antigens. These high specificity McAbs and some of new high specificity McAbs generated during the early stages of the proposed grant period will be utilized to achieve the objectives described above. We wish to test the validity and limit of the widely accepted hypothesis that individual types of human leukemias represent a frozen state ("maturation arrest") of clonal cells at different stages of normal hematopoietic cell differentiation. Our two unique T cell leukemia antigens TALLA (T acute lymphoblastic leukemia antigen) and GP37 defined by McAbs SN1 and SN2, respectively, present to us unique opportunities to test this hypothesis because our evidence strongly indicates that these antigens are not normal differentiation antigens. Furthermore, our recently discovered novel non-T leukemia associated antigen, termed GP160, appears to provide us with an important opportunity to investigate the target cells for leukemogenesis as well as to test that "maturation arrest" hypothesis.